tbuckley/cabot-search huggingface dataset:
Abstract P170: The Association of Urinary Cadmium and Zinc With Lower Extremity Amputations. Evidence From the Strong Heart Study
Authors: Marta Galvez-Fernandez, Kishan A Bhatt, Filippo Ravalli, Walter Goessler, Ying Zhang, Amanda M Fretts, Jason G Umans, Tiffany Sanchez, Francisco Ujueta, Gervasio A Lamas, Richard R Fabsitz, Ana Navas-Acien
Journal: Circulation (2023)

Background: Cadmium is a cardiotoxic divalent metal that accumulates in the liver and kidney. It resembles the essential metal zinc, replacing it in numerous enzymes and proteins. Zinc plays a major role in insulin function. Glucose dyshomeostasis increases the loss of zinc through the urine. Cadmium has been associated with peripheral artery disease and critical limb ischemia, conditions that lead to limb amputations. Chelation treatment with edetate disodium, an agent that facilitates the excretion of cadmium from the body, was beneficial for individuals with critical limb ischemia and diabetes in several small studies. This study evaluated the association of urinary levels of cadmium and zinc with amputations in a population with a high burden of diabetes from Arizona, Oklahoma, North Dakota and South Dakota. Hypothesis: We hypothesize that urinary cadmium and zinc levels are related to prevalent amputations in the SHS cohort. Methods: We included 2,724 participants from the Strong Heart Study, a population-based cohort study in 12 American Indian communities, recruited in 1989-1991 and followed for amputations through 1998-1999. Trained staff identified amputations of the lower extremity through visual examination at the baseline visit. We censored traumatic amputations. Baseline metal levels in spot urine samples were divided by urinary creatinine to account for urine dilution. Results: Mean age was 56.4 years, 41.5% participants were male, and 42% had diabetes. We identified a total of 35 (1.3%) amputations of the lower extremities during the study period. Median urinary levels were 0.97 μg/g for cadmium and 0.56 mg/g for zinc. Higher levels of urinary cadmium and zinc were positively associated with the presence of amputations. The odds ratios of prevalent amputations for an IQR of cadmium and zinc distribution were 1.54 (1.00, 2.38) and 2.24 (1.48, 3.39), respectively, in models adjusted for sociodemographic, lifestyle (tobacco and alcohol intake), and other factors (BMI, hypertension and diabetes status, HDL and LDL-cholesterol, and estimated glomerular filtration rate). The associations remained after further adjustment for fasting plasma glucose levels. Urinary cadmium and zinc levels were positively correlated (r=0.24, P&lt;0.001). Conclusions: Urinary cadmium and zinc were positively associated with the presence of lower extremity amputations in American Indian adults with a high burden of diabetes. These results support the current evidence of cadmium as a cardiometabolic risk factor, and the potential role of impaired zinc metabolism, reflected as increased urinary zinc excretion, in vascular complications of diabetes.
Abstract P176: The Association of Blood Urea Nitrogen With Incident Heart Failure in the Community: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Hairong Liu, Junichi Ishigami, Lena M Mathews, Suma H Konety, Michael E Hall, Patricia Chang, Chiadi E Ndumele, Wayne D Rosamond, Kunihiro Matsushita
Journal: Circulation (2023)

Background: Blood urea nitrogen (BUN) has been shown as a potent predictor of morbidity and mortality in patients with heart failure (HF). Whether BUN levels are associated with incident HF in the general population is unknown. Methods: Among 14,263 ARIC participants without a history of HF at baseline (1987-1989) (mean age 54 [SD 5.7] years, Female 54.4%, Black 25.4%), we assessed the association of BUN with incident HF. BUN levels (mg/dL) were divided by quartiles in the primary analysis, and the highest quartile was further divided into tertiles in the secondary analysis (Q1&lt;13, Q2 13-15, Q3 15-17, Q4a 17-19, Q4b 19-21, Q4c &gt;21). We defined HF as hospitalization or death with HF diagnosis and estimated hazard ratios (HRs) using multivariable Cox regression models. Results: During a median follow-up of 26.2 years, 3,506 participants developed incident HF (incidence rate 10.7 per 1,000 person-year). When we adjusted for demographic variables, using the lowest quartile (Q1) as the reference, the top quartile (Q4) showed an HR of 1.18 (95% CI 1.08, 1.10) (Model 1 in Table ). When we subdivided Q4, Q4c showed the highest HR (1.40 [95% CI 1.21, 1.61]). The association was similar after further adjusting for lifestyle and other clinical factors (Model 2 in Table ). Further adjustment for estimated glomerular filtration rate modestly attenuated the association (Model 3 in Table ), but HRs remained significant for Q4 as a whole (1.11 [1.01, 1.22]) and Q4c (1.27 [1.09, 1.47]). In subgroup analysis, the association was stronger in Black participants than in White participants (p-for-interaction &lt;0.05). Conclusion: In this community-based cohort, higher BUN levels were significantly associated with incident HF. BUN levels are often measured as part of routine clinical care and thus may inform clinicians to identify individuals at risk of HF, particularly in resource-constrained settings with limited availability of measuring HF-specific markers such as natriuretic peptides.
Abstract 38: A Novel Two-Question Antihypertensive Medication Adherence Scale Predicts Blood Pressure Control and Cardiovascular Disease Outcomes
Authors: Farah Allouch, Erin Peacock, Katherine T Mills, Paul K Whelton, Jing Chen, Jiang He
Journal: Circulation (2023)

Introduction: Poor medication adherence is a major contributor to uncontrolled hypertension, the leading preventable risk factor for CVD and mortality worldwide. Simple and accessible tools are needed to quantify medication adherence. We developed a novel two-question adherence scale in the Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS) trial and tested its prediction of BP control and CVD. Methods: We collected data on the IMPACTS Medication Adherence Scale (IMPACTS-MAS) and the eight-item Morisky Medication Adherence Scale (MMAS-8) in 1,206 IMPACTS participants. The IMPACTS-MAS consists of two questions, (1) “Over the last 7 days, on how many days did you not take any BP pills”, and (2) “Over the last 7 days, on how many days did you cut back on your BP pills?” and is categorized as low or high adherence. Linear and logistic mixed effects regressions examined the association between IMPACTS-MAS, MMAS-8, and uncontrolled BP. We also assessed IMPACTS-MAS in 33,995 China Rural Hypertension Control Project (CRHCP) participants studied at baseline and followed for CVD outcomes during a 36 month period. Cox regression examined the association between IMPACTS-MAS and CVD outcomes adjusting for treatment group, age, sex, education, and history of CVD. Results: The IMPACTS participants had an average age of 58 years and 56% (676/1,206) were female. Compared to high adherence, low adherence on IMPACTS-MAS and MMAS-8 was associated with 3.5 (95% CI: 1.9,5.1) and 2.6 (1.1,4.1) mmHg higher SBP , 2.5 (1.3,3.7) and 2.0 (0.87,3.1) higher DBP , and 73% [OR=1.73 (1.27,2.36)] and 68% [OR=1.68 (1.27,2.23)] higher uncontrolled BP (≥140/90 mmHg), respectively. The CRHCP participants had an average age of 63 years and 61% (20,825/33,995) were female. Compared to high adherence, low adherence on IMPACTS-MAS was associated with 3.6 mmHg (3.2,4.0) higher SBP , 0.89 mmHg (0.76,1.0) higher DBP , and with 42% [OR=1.42 (1.37,1.47)] higher uncontrolled BP , during follow-up. Further, low adherence was associated with 53% [HR=1.53 (1.30,1.81)] higher levels of CVD , 88% [HR=1.88 (1.11,3.17)] higher levels of myocardial infarction , and 54% [HR=1.54 (1.28,1.86)] higher levels of stroke during follow-up. Finally, low adherence was associated with 51% [HR=1.51 (1.31,1.75)] higher levels of CVD death and 47% [HR=1.47 (1.31,1.65)] higher levels of all-cause mortality , during follow-up. Conclusion: The novel two-question IMPACTS-MAS score is associated with BP control and predicts CVD outcomes and mortality in diverse populations. It is a simple, accessible tool that can be used in research and clinical practice to identify medication nonadherence.
Abstract P158: Intake of Chocolate by Subtypes and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies
Authors: Binkai Liu, Lu Zhu, Yang Hu, Joann E Manson, Qi Sun
Journal: Circulation (2023)

Backgrounds: Cocoa and cocoa flavonoids may exert health benefits including improving insulin sensitivity and lowering type 2 diabetes (T2D) risk. Previous studies have reported inverse associations between chocolate consumption and T2D risk, although it is largely unknown regarding whether the associations differ between dark chocolate and milk chocolate. The objective of this study is to prospectively examine the associations between the consumption of dark chocolate, milk chocolate, and total chocolate, and the risk of T2D, in three large cohort studies with repeat dietary measurements over 10 years of follow-up. Methods: Data from three prospective cohorts in the United States were used, including Nurses’ Health Study (2006-2020), Nurses’ Health Study II (2007-2019), and Health Professionals Follow-Up Study (2006-2020). Dark and milk chocolate consumption information was assessed at baseline and updated every 4 years through a validated food frequency questionnaire. Chocolate consumption was categorized into 4 groups: never or &lt;1 serving/month, 1 serving/month to 1 serving/week, 1-4 servings/week, and ≥5 servings/week. Self-reported T2D cases were confirmed using a supplementary questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between total, dark, and milk chocolate intake, and the risk of T2D. Results: After adjusting for lifestyle and dietary risk factors for diabetes, compared to participants who never or rarely eat chocolate, those who consumed any chocolate ≥5 servings/week had a 22% (95% CI: 10% to 32%; p for trend = 0.0003) lower rate of T2D. For dark chocolate, those who consumed ≥5 servings/week had a non-significant 16% (95% CI: -2% to 31%; p for trend = 0.005) lower rate of T2D than those who never or rarely eat dark chocolate. The associations between milk chocolate intake and T2D risk are largely null. Spline regression shows an L-shaped non-linear dose-response relationship between total chocolate intake and the risk of T2D (p=0.02 for curvature). The risk reduction plateaus when the total chocolate intake is higher than 5 servings/week. There is a linear dose-response association between dark chocolate intake with the risk of T2D (p=0.006 for linearity). Conclusion: Higher consumption of total chocolate and especially dark chocolate was significantly associated with a lower risk of type 2 diabetes. These findings support the potential cardiometabolic benefits of consuming chocolates that are rich in flavonoids.
Abstract P457: Healthful Lifestyle Factors and Incidence of Early Onset Cardiovascular Disease in the Million Veteran Program
Authors: Eiman Elhouderi, Xuan-Mai Nguyen, Yanping Li, Kelly Kim, Rachel Ward, PETER WILSON, John M Gaziano, Luc Djousse on behalf of the VA Million Veteran Progra
Journal: Circulation (2023)

Background and Objective: While previous studies have reported benefits of healthful and modifiable lifestyle factors on the incidence of cardiovascular disease (CVD) among adults, it is unclear whether adhering to healthful lifestyle factors is associated with a lower risk of CVD among young adults. Thus, the purpose of this study is to examine the association of low-risk lifestyle factors including normal weight, regular exercise, not smoking, adequate sleep, and a healthy diet with risk of early onset CVD in the Veterans Affairs (VA) Million Veteran Program (MVP). Methods: The study cohort included 49,603 MVP participants with self-reported and electronic health records information on the five low-risk lifestyle factors. Assigning values to each lifestyle factor, we created a score that ranges from 2 to 15 with higher scores indicating a healthier lifestyle. The association between low-risk lifestyle factors and fatal and non-fatal CVD was assessed using Cox proportional hazard model adjusted for age, sex, race, education, income, marital status, alcohol use, total energy intake, diabetes, hypertension, and hypercholesterolemia. Results: The mean age was 47 years and 37 % were women. After a follow-up period of 3.1 years, we documented 655 early onset CVD events with an overall crude annual incident rate of 3.5‰ among women and 3.9‰ among men. In Cox proportional hazard model adjusted for confounders, a higher low-risk lifestyle score was associated with a lower risk of early onset CVD [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.33-0.56, comparing extreme score, Figure]. Conclusion: Our data show an inverse and graded association of healthful lifestyle factors with risk of early onset CVD among young veterans, suggesting that adherence to low-risk lifestyle factors including not smoking, sufficient sleep, normal weight, and regular exercise may help prevent early onset CVD.
Abstract P183: Systolic Dysfunction is Associated With Increased Occurrence and Worse Outcomes of Periprocedural Cardiovascular Adverse Events After Transcatheter Aortic Valve Replacement
Authors: Dennis Kumi, Edwin Gwira-Tamattey, Ufuk Vardar, Birju Patel, Sadichhya Karki
Journal: Circulation (2023)

Background: Transcatheter aortic valve replacement (TAVR) rate continues to ascend nationwide as per the transcatheter valve therapy registry, and this calls for even better strategies to aim for negligible complication rates. Current practice relies on surgically derived risk models. We set out to assess the impact of systolic dysfunction on perioperative cardiovascular adverse events. Hypothesis: The presence of systolic dysfunction is associated with increased frequency and poorer outcomes of periprocedural cardiovascular adverse events among patients undergoing TAVR. Method: A retrospective cohort study was designed using data obtained from the 2016 to 2018 combined National Inpatient Sample (NIS) database. The current procedural terminology (CPT) Codes of ICD-10 were used to identify patients admitted for TAVR. They were then dichotomized into two cohorts based on the presence of systolic dysfunction. Primary outcomes were death, length of stay, total charge, composite of all cardiovascular perioperative adverse events and composite of all cardiovascular perioperative adverse events and death. Secondary outcomes were individual cardiovascular perioperative adverse events for all TAVR admissions and subsequently for patients with post-TAVR cardiac dysfunction. Multivariate linear and logistic regressions were used to adjust for confounders. Results: There was a total of 145,640 admissions for TAVR among whom were 16,980 with systolic dysfunction. Details of outcomes of study are summarized in table 1 below. Conclusion: Among inpatients who underwent TAVR, systolic dysfunction is associated with higher odds of mortality, composite of all cardiovascular adverse events and composite of death and all cardiovascular adverse events. There was increased odds of periprocedural cardiac dysfunction, particularly with increased cardiogenic shock. There was increased length of stay and total charge.
Abstract P470: Total Plaque Area and Association With Stroke Risk Factors in a Native American Population
Authors: Kevin V Thomas, Stephanie M Wilbrand, Timothy Hess, Jenna Maybock, Yurim Lee, Brady Kerwin, Melissa Metoxen, Debra Danforth, Amanda Riesenberg, Robert J Dempsey, Carol Mitchell
Journal: Circulation (2023)

Objective: Total plaque area (TPA) has been associated with stroke risk factors; however, it has not been well studied in a Native American population. The objective of this study is to examine the relationship of TPA with stroke risk factors (RF). Methods: Participants enrolled in the “Stroke Prevention in the Wisconsin Native American Population” (n=119) underwent a health history risk assessment, cognitive testing, carotid ultrasound to measure TPA, and a meeting with a health wellness coach. TPA for each participant was measured using the LifeQ Medical Plaque Analysis Software (Nicosia, Cyprus). Statistical analyses were performed using SPSS (SPSS, IBM Corporation, Armonk, NY, USA) and SAS (SAS Institute Inc., Cary, NC, USA). Descriptive statistics for continuous variables are reported as the median and interquartile range (IQR). Spearman rho correlation was used to examine relationships between total plaque area and stroke risk factors. Robust M—estimation was used to examine which risk factors predicted TPA after adjustment for other covariates. Results: Of the 119 participants, 22 (18.5%) had no plaque and 97 (81.5%) had plaque, 100 (83.3%) were identified as high-risk (≥55 years with three risk factors for stroke) and 19 (15.8%) low-risk (≥55 years with fewer than three risk factors for stroke). Median participant age was 65 (IQR=11.0) years of age, 78.3% female. In univariate analyses, TPA was significantly associated with age (r s =.259;p=.005) and body mass index (BMI) (r s =-.300;p&lt;.001). In a multivariable robust M-estimation model (including age, sex, BMI, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, hemoglobin A1c, physical activity, and categorical variables (yes/no) current smoker, history of high cholesterol, coronary artery disease, diabetes, hypertension, and transient ischemic attack), only age (p=.03), sex (p=.012), and hemoglobin A1c (p=.028) remained significant for predicting total plaque area (r 2 =16.5%). Conclusion: Multivariate analysis demonstrated that age, sex, and hemoglobin A1c predicted TPA. Further work is needed to understand how both traditional and non-traditional stroke RFs may affect the risk of stroke in Native Americans.
Abstract P167: Residential Exposure to Greenness and Mortality Following Percutaneous Coronary Intervention
Authors: Saar Ashri, Gali Cohen, Lihi Golan, David Broday, David M Steinberg, Rakefet Shafran-Nathan, Guy Witberg, Tamir Bental, Lital Keinan-Boker, Mika Moran, Ran Kornowski, Yariv Gerber
Journal: Circulation (2023)

Background: Evidence regarding environmental exposure to green spaces and outcomes in coronary disease patients is lacking. We evaluated the association between residential exposure to greenness and mortality in patients undergoing percutaneous coronary interventions (PCI). Methods: Consecutive patients undergoing PCI at the Rabin Medical Center in Israel between 2004-2014 (n = 12,104) were studied. Clinical data at the time of hospitalization were extracted from medical records. Mortality data (through 2017) were obtained from the Ministry of Health. Patients with incomplete information on residential addresses were excluded. Exposure to greenness was estimated using normalized difference vegetation index (NDVI), a satellite-based index derived from Landsat 30 m spatial resolution imagery, with larger values indicating higher levels of vegetative density. NDVI was estimated within a buffer of 300 m around each patient’s home and as the point value of each 30 m pixel (immediate living environment). Additional residential-based environmental measures were obtained. Cox models assessed the hazard ratios (HRs) for mortality associated with greenness measures. Results: Among 11,262 patients analyzed [median age, 69 (IQR 61-78) y, 24% women], median NDVI-300 was 0.15 (IQR 0.13-0.17) and median NDVI-30 was 0.14 (IQR 0.11-0.17). Patients with higher NDVI-300 were slightly older; NDVI-30 was inversely correlated to ambient air pollution. During a median follow-up of 8.1 (IQR 5.1-10.6) years, 3,217 participants died. After adjustment for sociodemographic and clinical factors, NDVI-30 -but not NDVI-300- was associated with lower mortality (Figure), with an HR of 0.96 (95% CI: 0.92-0.99) per 1 SD increase. Conclusions: In this PCI registry, residential exposure to green spaces in the immediate living environment was associated with lower mortality. Results for the extended area of the living environment were inconclusive. This inconsistency between different spatial resolutions warrants further investigation
Abstract 01: Association of Copayment Level and Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter 2 Inhibitor Adherence in Diabetes and Heart Failure
Authors: Utibe R Essien, Balvindar Singh, Gretchen Swabe, Amber E Johnson, Lauren Eberly, Rishi Wadhera, Khadijah Breathett, Muthiah Vaduganathan, Jared W Magnani
Journal: Circulation (2023)

Introduction: Diabetes and heart failure (HF) rates are rising. Glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with improved outcomes in these conditions. Out-of-pocket cost may reduce medication adherence. We examined the association of medication copayment with 1-year adherence to these agents in individuals with diabetes and HF. Hypothesis: Individuals with high copayments have reduced adherence to GLP1RAs and SGLT2is. Methods: Using the Optum de-identified Clinformatics Data Mart Database, individuals with diabetes and HF and ≥12 months of enrollment with a GLP1RA or SLGT2i claim from 2014-2021 were included. We defined adherence as the proportion of days covered (PDC) ≥80%. We used multivariable logistic regression models to examine the adjusted odds of adherence by copayment level, defined as low (&lt;$10 USD), medium ($10-&lt;$50), and high (≥$50). Covariates included patient socioeconomic and clinical comorbidities. Results: We identified 94,610 individuals (age 61.8±11.4 years; 45.9% female) prescribed GLP1RAs or SGLT2is from 1/1/2014-9/30/2020, Overall, 39,149 individuals had a claim for a GLP1RA, of whom 25,557 (65.3%) had PDC ≥80%. In fully adjusted models, individuals with medium (adjusted odds ratio, aOR 0.61, 95% CI, 0.57-0.66) and high copayment (aOR 0.48, 95% CI, 0.44-0.51) were less likely to have PDC ≥80% with GLPRAs compared to those with low copayment ( Figure ). Overall, 51,072 individuals had a claim for an SGLT2i, of whom 37,339 (73.1%) individuals had PDC ≥80% at 1 year. Individuals with medium (aOR 0.67, 95% CI, 0.62-0.71) and high copayment (aOR 0.69, 95% CI, 0.64-0.74) were less likely to have PDC ≥80% with SGLT2is compared to those with low copayment. Conclusion: In a large cohort of individuals with diabetes and HF, 1-year adherence to GLP1RA or SGLT2i therapies was highest among individuals with low copayment. Improving adherence to guideline-based therapies requires interventions that reduce prescription costs.